KEY TERMS

calcitonin: a hormone made and released by the thyroid gland that lowers the level of calcium in the blood by stimulating the formation of bone

collagen: a protein found in bone and other connective tissues; collagen fibers are well suited for support and protection because they are sturdy, flexible, and resist stretch

hormones: molecules made in the body and released into the blood that act as chemical messengers for the regulation of specific body functions

matrix: in bone, the matrix is a solid nonliving material that is a composite of protein fibers and mineral crystals

osteoblast: a bone cell that can produce and form bone matrix; osteoblasts are responsible for new bone formation

osteoclast: a large bone cell that can destroy bone matrix by dissolving the mineral crystals

osteocyte: the primary living cell of mature bone tissue

tissue: a collection of similar cells that perform a specific function

STRUCTURE AND FUNCTIONS

Bones are active throughout life: the 206 bones of the skeleton establish the size and proportions of the body and interact with all other organ systems. Disorders of the skeleton can have profound effects on the other organ systems and serious health consequences for the organism.

Bone, or osseous tissue, contains specialized cells and a solid, stony matrix. The living cells found in bone account for less than 2 percent of the total bone mass. The unique hardened quality of the matrix results from layers of calcium salt crystals such as calcium phosphate, which is responsible for about two-thirds of a bone’s weight, and calcium carbonate.

Despite the great strength of the calcium salts, their inflexible nature means that they can fracture when exposed to sufficiently great bending or twisting forces or sharp impacts. Because the calcium crystals exist as minute plates positioned on a framework of collagen protein fibers, the resulting composite structure does lend a certain degree of flexibility to the bone matrix.

Based on the internal organization of its matrix, bone is classified as either compact (dense) bone or cancellous (spongy) bone. Compact bone is internally more solid, while cancellous bone is made from bony filaments (trabeculae) whose branching interconnections form a three-dimensional network. The bone marrow usually fills the cavities of the cancellous bone network, the primary location for blood cell formation in adults.

Both types of bone contain bone cells (osteocytes) living in small chambers called “lacunae,” found periodically between the matrix plates. Osteocytes provide the collagen fibers and the conditions for proper maintenance of the mineral crystals of the matrix. Microscopic channels (canaliculi) connect neighboring lacunae and permit the exchange of nutrients and wastes between osteocytes and accessible blood vessels.

Atypical skeletal bone has a central marrow cavity bordered by cancellous bone. The bone is enclosed by compact bone, and the outer surface is covered by periosteum. Periosteum consists of a fibrous outer layer and a cellular inner layer. The periosteum plays an important part in the growth and repair of bone, and it is the attachment site for muscles. Collagen protein fibers from the periosteum interconnect with the collagen fibers of the bone.

The marrow cavity inside the bone is lined by endosteum. Endosteum is an incomplete layer covering the trabeculae of cancellous bone and contains various types of cells. The endosteum also plays important roles during bone growth and repair.

The bone matrix is not an unchanging, permanent structure. The bone matrix is constantly dissolved during a person’s life while the new matrix is synthesized and deposited. Approximately 18 percent of bone protein and mineral constituents are replaced each year. Such bone remodeling can result in altered bone shape or internal rearrangement of the trabeculae. It may also result in a change in the total amount of minerals stored in the skeleton. These processes of bone demineralization (osteolysis) and new bone production (osteogenesis) are precisely regulated in the healthy individual.

An osteoclast is the type of bone cell responsible for dissolving the mineralized matrix. The osteoblasts are the cells that produce the materials that later become the bony matrix. The activities of these cells are influenced by several hormones and the physical stress forces to which a bone may be exposed, such as when a particular muscle becomes stronger as the result of weight training and pulls more strongly on the bones to which it is attached. Increased stress forces on a bone result in that bone becoming thicker and stronger, thereby allowing the bone to withstand the stresses better and reducing the risks of bone fracture. When bones are not subjected to ordinary stresses, such as in persons confined to bed or in astronauts living in microgravity conditions during space flight, there is a corresponding loss of bone mass, with the unstressed bones becoming thinner and more brittle. After several weeks in an unstressed state, a bone can lose nearly a third of its mass. Following the resumption of normal loading stresses, the bone can regain its mass just as quickly.

The skeleton has five major functions: support for the body; protection of the soft tissues and organs; leverage to change the direction and size of the muscular forces; blood cell production, which occurs within the red marrow residing in the marrow cavities of many bones; and storage of both minerals (to maintain the body’s important reserves of calcium and phosphate) and fats (in yellow marrow to serve as an important energy reserve for the body).

The human skeleton contains 206 bones. These are distributed between two subdivisions of the skeleton: the axial skeleton and the appendicular skeleton. The axial skeleton contains eighty bones distributed among the skull (twenty-nine bones), the chest (twenty-five bones), and the spinal (vertebral) column (twenty-six bones). The remaining 126 bones are found in the appendicular skeleton’s components: four bones in the shoulder (pectoral) girdles, sixty bones in the arms (including the fifty-four bones located in both of the hands and wrists), two bones in the hip (pelvic) girdle, and sixty bones in the legs (including the fifty-two bones found in the ankles and feet).

Image via Wikimedia Commons. [Public domain.]

Skeletal bones are classified according to their shape. Short bones are cuboid in shape and are found in the wrist and the ankle. Long bones occur in the upper arm, the forearm, the thigh, the lower leg, the palm, the fingers, the sole of the foot, and the toes. Flat bones form the top of the skull, the shoulder blade, the breastbone, and the ribs. Sesamoid bones are typically small, round, and flat. They are found near some joints, such as the kneecap on the front of the knee joint. Irregular bones have shapes that are difficult to describe because of their complexity. Examples of irregular bones are found in the spinal column and the skull.

Learning to name the bones solely by their appearance is made somewhat easier because each one has a definitive form and distinctive surface features. Where blood vessels and nerves enter a bone or lie along its surface are commonly discernible as indentations, grooves, or holes. The locations where muscles are connected to bones by tendons or where a bone is tethered to another bone by ligaments are often visible as elevations, projections, or ridges of the bony matrix or as roughened areas on the surface of the bone. Finally, the areas of the bone that are involved in forming joints (articulations) with other bones have characteristic shapes that impart specific properties to the joint. Various specialized terms are used to name these features.

The joint’s anatomy determines its functional capability, and the parts of the bones that form the joint have distinctive structural features. Articulations are found wherever one bone meets another. The amount of motion permitted between the bones forms an articulation range from none (for example, between the skull bones) to considerable (as at the shoulder joint).

DISORDERS AND DISEASES

Among the skeleton disorders, several of them occur during the growth and development of the bones. The problems usually result in abnormal (most often decreased) stature or abnormal shape of the bones. The aberrations may alter the entire skeleton or be restricted to a portion of it. The basis of the pathology is to be found in a disruption of the normal, orderly sequence of events that take place during the growth and remodeling of the bones.

Image via Wikimedia Commons. [Public domain.]

Osteopetrosis belongs to this class of disturbance. It is an inherited condition in which abnormal remodeling increases bone density. Osteopetrosis seems to result from a reduced activity level by the cells responsible for dissolving the bone matrix—the osteoclasts. There is a precisely regulated relationship between osteoclast and osteoblast activity in healthy, normal individuals. Depending on the body’s current needs, or merely those of a single bone, the rate of bone matrix formation by osteoblasts may be greater than, equal to, or less than the rate of bone resorption by osteoclasts.

Osteoclasts are derived from cells that are made in the bone marrow. For this reason, bone marrow transplantation has been tried as a treatment for osteopetrosis; however, this approach is risky and not always successful. There has also been improvement in the condition of some osteopetrosis patients following treatment with a hormone related to vitamin D. This particular hormone can increase bone resorption and thereby may prevent the increase in bone density that characterizes this condition.

Another member of this category of disturbance is congenital hypothyroidism. This condition can be caused by an insufficient supply of the element iodine in the pregnant mother, or it may result from inherited errors in producing the thyroid hormones. The basic problem in this condition is underactivity of the thyroid gland during the development of the fetus, resulting in a decrease in the production of thyroid hormones in the fetus.

Among the organ systems seriously affected by this condition is the skeleton. The bones do not develop correctly; consequently, the bones are shorter and thicker than normal, with corresponding changes in the child’s appearance. Early diagnosis of the condition and timely treatment with drug forms of thyroid hormones can halt the disease. Otherwise, the adult skeleton has stubby arms and legs, a somewhat flattened face, and a disproportionately large chest and head.

A pituitary gland disorder can result in skeletal development abnormalities that are opposite to those observed in congenital hypothyroidism: namely, excessive growth in the length of bones. This condition is called “giantism” (or gigantism). It results from the overproduction of growth hormone by the pituitary gland before normal adult stature has been achieved. Cases are known of people attaining heights of more than eight feet tall. Unfortunately, because of complications involving other organ systems due to the excessive production of growth hormone, the persons suffering from this disorder usually die before the age of thirty. The most common cause of this situation is a tumor in the pituitary gland.

Surgical removal of the pituitary tumor is often attempted. Successful tumor removal stops growth hormone overproduction. In other cases, radiation treatments are used to destroy the tumor. It is also possible to combine both treatment techniques. Drug therapy is also possible. Because of the high doses necessary and the accompanying side effects of high drug dosages, however, the reduction of growth hormone levels through drug treatment is usually applied only in conjunction with one or both other therapies.

Some disorders afflict adult bone. Most of the remodeling disorders involve a loss of bone mass. The group of disorders known as “osteoporosis” (porous bone) is a rather common example; according to the International Osteoporosis Foundation, by 2013, osteoporosis affected more than 200 million people worldwide. The reduction in bone mass is sufficient to result in increased fragility and ease of breakage. There is also slower healing of bone fractures. In advanced cases, bones have been known to break when the person sneezes or rolls over in bed.

Loss of bone mass is a normal feature of aging, becoming quite marked after seventy-five, particularly in the hip and leg bones. Because of the normal decrease in bone mass with aging, there is no clear distinction between normal, age-related skeletal changes and the clinical condition of osteoporosis. The occurrence of excessive fragility at a relatively early age is an indication that osteoporosis is developing. Normally, between the ages of thirty and forty, the activity of the osteoblast cells (those that form the bone matrix) begins to decrease. In contrast, the osteoclast cells (those that dissolve the matrix) maintain their previous activity level. This imbalance between osteoclast and osteoblast activities results in the loss of about 8 percent of the total bone mass each decade for women and about 3 percent for men. Because of unequal loss in the different skeletal regions, the outcome is gradual height reduction, teeth loss, and fragile limb development.

Osteoporotic bones are indistinguishable from normal bones concerning their bone composition. The problem is too little of the strength-imparting matrix, with both compact and spongy bone being affected.

There are multiple causes of osteoporosis. Some cases have no known cause (idiopathic osteoporosis), some are inherited, and others are brought about because of hormonal (endocrine) disorders, vitamin or mineral deficiency, or effects of the long-term use of certain drugs.

The fact that women are more often affected than men and that the process is most conspicuous in women beyond menopause has implicated the female sex hormones (and, specifically, their decreased production) in the initiation of the osteoporotic process. One form of therapy is the administration of certain female sex hormones (specifically estrogens) to postmenopausal women (who have decreased production of estrogens). This treatment slows their loss of bone mass. While hormone therapy has been the mainstay of osteoporosis treatment for many years, controversy regarding the risks of hormone therapy has caused many women to stop using this treatment altogether. In 2002, two major studies found that the risks associated with hormone therapy outweigh the benefits. Following these studies, doctors began to look closer at the roles that high-impact exercise and the use of calcium and vitamin D play in decreasing bone density loss.

Other osteoporosis treatments include specific medications, such as bisphosphonates, recombinant parathyroid hormones, and monoclonal antibodies that influence bone deposition and resorption. The five main bisphosphonates are alendronate, ibandronate, pamidronate, risedronate, and zoledronate. These drugs bind to the hydroxyapatite matrix in the bone. When osteoclasts degrade bone, they also take in the bisphosphonates, which poison the osteoclast’s metabolism. Bisphosphonates, therefore, diminish bone resorption. Daily subcutaneous injections of parathyroid hormone mimics stimulate bone formation. These drugs include Teriparatide (Forteo and others) and abaloparatide (Tymlos). Both medications are Food and Drug Administration (FDA)-approved to treat osteoporosis for up to two years in postmenopausal women at high risk for fracture. Denosumab is a human monoclonal antibody that binds the RANKL protein, preventing RANKL from binding to RANK receptors on the surface of osteoclasts precursors. RANKL inhibition prevents the activation and maturation of osteoclasts, which limits bone breakdown. Denosumab (Prolia, Xgeva) is injected subcutaneously every six months to treat postmenopausal osteoporosis. This drug also treats cancers that metastasize to bone, but it is administered once a month in such cases. The newest osteoporosis medicine is romosozumab (Evenity). This monoclonal antibody binds to and inhibits a bone-specific signaling protein called “sclerostin.” Sclerostin inhibition increases bone formation and decreases bone resorption. The FDA approved romosozumab for the once-monthly subcutaneous treatment of osteoporosis. The newness of this drug caused the FDA to only approve its use for up to one year in osteoporotic women who did not respond to or could not tolerate other drugs.

Women at risk for osteoporosis and breast cancer have other options for their treatment. Raloxifene (Evista and generics) is a selective estrogen receptor modulator (SERM). This drug has estrogen-like effects on bones but antiestrogen effects on the uterus and breast. Raloxifene reduces the risk of invasive breast cancer and increases bone density. It provides a good treatment option for women with osteoporosis who have a high risk for invasive breast cancer.

Regular exercise is a means both of preventing the onset of osteoporosis and slowing its progression. Because muscular activity is critical for maintaining bone mass, extended periods of inactivity or immobilization can induce osteoporosis. For women, it is known that the amount and regularity of their exercise during their teenage years is strongly associated with their chances of developing osteoporosis thirty and more years later. The exercise need only be of moderate intensity to significantly decrease the risk of developing osteoporosis. Indeed, exercise at a level of intensity so high that it interferes with the normal female menstrual cycle (stopping the occurrence of menstruation completely or causing irregular cycle lengths) can increase the risk of developing osteoporosis later in life.

PERSPECTIVE AND PROSPECTS

One of the bone’s primary functions is the protection of softer, more vulnerable tissues and organs. The physical properties of bone—it is as strong as cast iron but only weighs as much as an equally large piece of pinewood—make it ideal for this job. This combination of strength and lightness derives from the bony matrix of mineral crystals and the architecture of the bone, which unites compact and spongy bone.

The physical and chemical properties of the mineral crystals also result in the permanency of bone following death. Often the only trace of a dead body is the skeleton. Because of the resistance of bone to the processes of decomposition that befall the other tissues of the body following death, investigators are often able to determine the sex of the person whose skeleton has been found, even though all other tissues have long since disappeared. This identification is possible because of the characteristic differences between male and female adult skeletons. Racial differences in the detailed structure of the skull and pelvis, age-related changes in the skeleton, signs of healed bone fractures, and the prominence of ridges where muscles attach (giving clues about the degree of muscular development) are also valuable sources of information when attempting to identify skeletal remains.

The sexual differences in the human skeleton are most obvious in the adult pelvis. These are genetically determined differences that are structural adaptations for childbearing. For example, the pelvis is smoother and wider in females than in males. Other differences include a lighter and smoother female skull, a more sloping male forehead, a larger and heavier male jawbone, and generally heavier male bones that typically possess more prominent markings.

Among the common age-related changes found in skeletons are a general reduction in the mineral content and less prominent bone markings, which become more obvious after about age fifty. Various bones in the skull fuse together at characteristic ages ranging from one to thirty years of age. Examination of other bones throughout the body can also provide more accurate estimates of the age of a skeleton at the time of death.

Another consequence of the permanent nature of bone is that it provides a record of the changes in the skeletal anatomy of humans that have occurred during the hundreds of thousands of years of human evolution. Expert examination of skeletal remains can reveal an amazing wealth of information concerning the health and even the deceased’s lifestyle.

Further Reading